Tuning the hybridization properties of modified oligonucleotides: from flexible to conformationally constrained phosphonate internucleotide linkages

0475163 - ÚOCHB 2018 RIV GB eng J - Journal Article
Páv, Ondřej - Barvík, I. - Liboska, Radek - Petrová, Magdalena - Šimák, Ondřej - Rosenbergová, Šárka - Novák, Pavel - Buděšínský, Miloš - Rosenberg, Ivan
Tuning the hybridization properties of modified oligonucleotides: from flexible to conformationally constrained phosphonate internucleotide linkages.
Organic & Biomolecular Chemistry. Roč. 15, č. 3 (2017), s. 701-707. ISSN 1477-0520. E-ISSN 1477-0539
R&D Projects: GA ČR GA13-26526S; GA MZd NV15-31604A
Institutional support: RVO:61388963
Keywords : molecular dynamics simulations * sugar phosphate backbone * nucleic acid recognition
OECD category: Organic chemistry
Impact factor: 3.423, year: 2017

The concept of conformational restriction leading to the preorganization of modified strands has proven to be successful and has afforded nucleic acid analogues with many interesting properties suitable for various biochemical applications. We utilized this concept to prepare a set of constrained oligonucleotides derived from 1,4-dioxane and 1,3-dioxolane-locked nucleoside phosphonates and evaluated their hybridization affinities towards their complementary RNA strands. With an increase of Delta T-m per modification up to + 5.2 degrees C, the hybridization experiments revealed the (S)-2', 3'-O-phosphonomethylidene internucleotide linkage as one of the most T-m-increasing modifications reported to date. Moreover, we introduced a novel prediction tool for the pre-selection of potentially interesting chemical modifications of oligonucleotides.
Permanent Link: http://hdl.handle.net/11104/0272011